I think part of the reason I'm having eye trouble lately -- just part of the reason -- is perhaps due to copper, or 'biovavailable' copper being released as I increase my zinc (which is needed to convert beta carotene and retinol to retinal in the eyes). I'm really not certain. My NutraEval copper was low, and also low in hair analysis, but was told by these hair 'experts' that I had high 'hidden' copper stores in my liver. I do know of another person who had bad eye issues until she lowered her copper (which also was supposedly high).

?????? !!!

p.s. The only reason I tend to give some credence to the hair analysis theory, is that whenever I took a copper supplement -- especially the last few times -- my anxiety, overstimulation, etc., increased big time. Made me feel I was going to lose it completely...

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Wow! Thanks for that piece of the puzzle! I did not know zinc was needed to convert beta-carotene to retinal! I had come to the conclusion that I was genetically unable to convert beta-carotene to Vitamin A but now it looks like it could be just another side-effect of my allergies using up all the damn zinc! And yes I do have eye issues...like a dry eye issue...when there is cold dry air which causes me allergies...all goes away when the temp rises above 32.
Do your eye issues go away as the weather improves?

Mine are just starting to improve (off and on) by using evening primrose oil (around my eyes, just a little bit) and as a supplement, plus krill, and will try some sort of EFA combination very soon. I had this happen late 2009-early 2010, and back then I was going to a low-cost acupuncture clinic -- and several of them said (TCM-wise) it was due to either "liver blood deficiency" and/or "liver yang rising" -- i.e., too much yang, not enough yin. But I was probably considerably deficient in zinc back then -- when I first did the Zinc Tally (taste) test in the summer of 2011, it tasted like pure water. My sister took a spoonful...and it had a strong metallic taste, which it should, if one has enough zinc.

I didn't know about the zinc-retinal connection until about 3 weeks ago myself. Desperate times call for desperate googling...

p.s. Plus, I should've gotten new glasses 4-5 years ago, but being on Medicaid, it's next to impossible (and now IS impossible) to find a place that will provide the actual glasses. But a friend has offered to pay for them, so I'm heading to the eye doctor on Friday........been squinting for years.

Can you explain this section a bit more? Trying to understand why your folate deficiency symptoms got worse. Also specifically which symptoms were attributed to the folate deficiency assuming everything else was in place. I am assuming you had no methyl trap, correct? As you were on active B12s? Just trying differentiate ATP dysfunction from folate and / or b12 deficiency.

I am confused. Of course the brain / neurons have active Krebs cycle going. You seemed to be implying that the Krebs cycle is a fatty acid only metabolic pathway.

A main source of the aerobic Krebs cycle is glucose(+ oxygen). That is at the heart of carboyhydrate metabolism. Glucose is turned into pyruvate via glycolysis inside of cells. Pyruvate then enters the Krebs cycle as oxacetalate. The brain can also get energy from ketosis (by converting ketones to acetyl COA) when needed in a pinch when blood sugar is low, but that is not strictly speaking fatty acid metabolism.

The brain dominantly uses the Krebs cycle based on carbohydrate metabolism. The brain cannot make use of fatty acids but can use ketones to help it when glucose is unavailable. However, the ketosis pathway does not need LCF to my knowledge. I suspect adb12 may be more about continued health of the mitochondria.

Just because there are indications of low B12 in certain neurodegenerative diseases does not in any way prove that neuronal mitochondria make heavy use of the methymalonic pathway as a primary energy source.

As an aside, for neurons, where there is some controversy is relevance of glucose (classical hypothesis) vs. the astrocyte-neuron lactate shuttle for certain types of neuron states. But that is probably not important to this discussion.

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Hi Dbkita,

Can you explain this section a bit more? Trying to understand why your folate deficiency symptoms got worse. Also specifically which symptoms were attributed to the folate deficiency assuming everything else was in place. I am assuming you had no methyl trap, correct? As you were on active B12s? Just trying differentiate ATP dysfunction from folate and / or b12 deficiency.

Once upon time back in the dark ages, for me in 2003, I started MeCbl all by itself. Not exactly all by itself, but, without AdoCbl, L-methylfolate or LCF. I was taking all the basics, vitamins, minerals and fats. In a backwards look I can see the layers. I had partial methylation block, methyltrap and partial ATP block at the start. I was skin and bones balloon all filled up wirh water and watery fat. I had to rest halfway up a flight of stairs. I needed help in the shower. I couldln't comb my hair or shave, arm and shoulder pain). I could barely brush and floss. When I started taking MeCbl I had incredibly intense neurological startup. I went from depressed to a realization "I could be happy now" in an hour.. The buring mouth and burning red tongue and and burning bladder stopped burning in 10 days, months longer to heal all the way. I regained a normalized sense of smell and taste. The lights literally came on that day have have stayed on since, going on 10 years now. Previously they stayed on several times for a few months during the desiccated liver trial. My burning muscles had the fire go out that first day and the burning subsided 100% in 10 days.

Mentioned at the time by me and orthers, was skin lesions. The acne type lesions started spreading and got much worse and infected. The IBS was terrible then because of food intolerances and IBS as such. The angular cheilitis got ever so much worse. So the methyltrap was broken but the partial methylation block was not. As I apparently do convert MeCbl to AdoCbl reasonably well (this is based on CURRENT understanding, at the time I thought anything not 100% effective was not good) and the partial ATP block reduced to about 75% of what it had been, enough to allow overdoing and crash and recrash. The partial methylation block remained in place. A person can have hypokalemia at the same time as partial methylation block in these reactions. They are not mutually exclusive.One layer can be healing and others breaking down at the same time.

Basically I went from constant mild folate specific symptoms to severe donut hole paradoxical folate deficiency. I took more folic acid but that didn't help at all and I had no idea at all. I focused on what I could affect. The inflammatory muscle pain continued or worsened. Joint pain worsened. MCS, asthma, allergies varied all over the place but didn't go away for several years more, after adding AdoCbl and 400mcg of methylfolate. That was when I started needing noticably more potassium. I think I was doing 200mg twice a day originally.

With just Mecbl added to basics, SACD continued to worsen, muscles contiuned to atrophy, edema and congestive heart failure continued to worsen. blood pressure WITH CoQ10 got dangerously high right away and I had to discontinue CoQ10 until AFTER the AdoCbl, LCF and Metafolin were in place (repairing the inferred cardiomyopathy of congestive heart failure). To start, or complete, tissue healing on all levels took the entire Deadlock Quartet.

The brain dominantly uses the Krebs cycle based on carbohydrate metabolism. The brain cannot make use of fatty acids but can use ketones to help it when glucose is unavailable. However, the ketosis pathway does not need LCF to my knowledge. I suspect adb12 may be more about continued health of the mitochondria.

If it DIDN"T use fatty acid chains, then the LCF would make no CNS difference much lass a massive energy difference. Further AdoCbl processes the fatty acids into the form needed for myelin repair in the brain and elevated CSF MMA wouldn't be apparent in Parkinson's, a suspected cause of Parkinson's. For people so afflicted AdoCbl and LCF make an unbelievably huge CNS difference in CNS healing and even many functional items.

Just because there are indications of low B12 in certain neurodegenerative diseases does not in any way prove that neuronal mitochondria make heavy use of the methymalonic pathway as a primary energy source.

Elevated CSF MMA in ALS and Parkinson’s and several others (I need to update that survey) is prominent. And the effects of AdoCbl and LCF is truly massive for Parkinson’s and” pseudo” or perhaps “pre”, Parkinson’s and affects dramatically dopamine and response in the limbic system. It’s practically a guided tour of the emotions of the limbic system. Even those not going down the Parkinson’s pathway, no MMA in the CSF, can have major response to CNS doses of AdoCbl and LCF. If a person has a specifc CNS response to MeCbl, most of those folks will have a major CNS response to AdoCbl ANDOR LCF. There are those with no significant MeCbl CNS response who will have massive CNS response to AdoCbl and LCF (down to below 1 mg total dose, HYPER response to minute oral doses of LCF). Your dismissal of this idea is a 100% missing the boat response. While it doesn’t prove anything, it is approximately 90+% predictable from symptoms. I don’t care what the diagnoses are. Those are very poor at predicting these responses generally. For those on the MeCbl & L-methylfolate pathway (SACD, MS) the response to AdoCbl & LCF is reduction of depression and relative euphoria. I call it relative euphoria because each level seems like “Ah, it feels so good that at last I feel good”. “Good” is relative. And that can happen at each step. Compared to feeling indescribably bad, feeling 0.25 better can be euphoric. A middle aged lady I know with MS tried these things, and did the worst possible thing. She danced exuberantly all evening and overdid it outrageously and crashed hard the next day. That is also predictable. I did the same thing over and over. It took me a year to get that tendency under control. Don’t increase distance walked by a mile. Just keep stepping it up at 50 feet a day. It is the most common cause of repeat crashes, feeling so good so suddenly that our common sense goes to the winds.

In order to form a set of hypotheses that allows one to heal, build a conditional system and model that assumes AdoCbl and LCF with omega3 fatty acids are absolutely critical to the brain affecting personality and moods rapidly. With this in place the understanding of what is happening in the brain with these various nutrients becomes predictable. Build the pragmatic model that works, then look to see why/how it works. I did check out each and every item in the literature before I added it. The difference is I interpreted severe side effects of certain kinds in a different way. The only “mistake” I made was glutathione. Everything else was dead on target. Without the extreme responses of myself and 9 others to glutathione I doubt that I would have recognized paradoxical folate deficiency. I built these items on one at a time, each one having to fit the model and prove it by working consistently on certain groups of symptoms. I build models and systems, not theories. My opinions and theories are just those. The point is I have adopted all sorts of theories and rejected others based on what fits. The model I have built is highly engineered, NOT THEORATIZED.

The sum total information on folic acid, CyCbl and HyCbl does not add up to anything that works predictably. The results on trials with these have been “disappointing” and presenting “conundrums” for 60 years. The model that I have built here, with all these weird ideas based on myself and others actually healing significantly in a predictable fashion is a completely different approach.

Instead of having a theory and throwing mud up on the wall and analyzing in microscopic detail and statistically saying “0.5% of people have an unexplainable hyper extreme response to LCF of an intolerable level of anxiety and had to be removed from the study. At only a 0.5% rate of such response it is just another side effect and matching placebo rates of anxiety and is only found in those with pre-existing anxiety and so can be safely ignored by prescreening for anxiety, if it isn’t a placebo effect”

I would say “Those people with a specific profile of symptoms including anxiety have a range of extreme responses to LCF at an approximately 95% predictable rate with a small percentage having this response unpredictably and a small percentage not having the predicted response of a mood sequence of anxiety, fear, panic, anger, rage, homicidal rage and severe depression over a 18 to 72 hour period. It is reproducible at will. Further refinement of the screening process may improve the selectivity.

Then when we get to Biotin which appears to be a “critical” cofactor because it can basically shut off ATP response by it’s relative deficiency or insufficiency. In these terms than being able to tolerate 4000mcg of biotin when some other critical cofactor is missing and that is no longer broken and biotin tolerance goes down to 1000mcg because it is NOW what then makes the difference, the most limiting factor. This is fits perfectly into the bottom up system I have been building. Then the next step is figuring out what is causing the shortage of biotin and test that. If that works, it kind of confirms the hypothesis and extends the system. Built piece by piece, from the bottom up leads to a working engineered system. It is also something I can walk into an HMO with and tie my compensation by obtaining specified results in XX% of people, based on indirect measures such as lowered pharmacy costs and less utilization all the way around on the selected persons.

You are working towards a different goal with different measures. I don’t have to prove a thing. All I am doing is to produce a system that is predictive of desirable results at a given or above a certain rate. Further the screening system must be cheap and a mass screening system. The AMA etc says in essence “testing everybody for b12 is not cost effective as it only finds 1% of population and they are expensive to treat forever with all the comorbidities”. 100% of that is based on folic acid, CyCbl and HyCbl. There is zero expectation that anybody will actually heal or reduce expenses. So detecting and treating b12 deficiency is very difficult, expensive and not worthwhile as they won’t really get well anyway unless you define that as getting MCV< 102 these days and maintain serum cobalamin level at or above 300pg/ml just before the next injection or with oral CyCbl tablets. By these definitions it is a complete surprise that mecbl and AdoCbl are completely unpredictable based on CyCbl and HyCbl experience.

Ok that makes sense. I understand more now. You are saying with only the methyb12 and other basics you ended up with some definite improvements in some ways but drove yourself into folate insufficiency that was made worse by folic acid and plant folates and only improved when you brought in sufficient levels of the deadlock quartet. Got it.

I think you are mixing two things up here to reach your conclusion. You are assuming that fatty acids are used directly in brain energy metabolism because you and others feel better and think better on LCF. The two are not necessarily linked.

Your brain / CNS and body are interconnected. If your body has more energy and vitality, your autonomic nervous system will be happier. And vice versa. There is often a false division when looking at clinical symptoms sometimes. The BBB prevents most fatty acids from getting across. The lipid regulation in the brain is very tight. Has to be. There are transport channels for choline and acetyl COA but not to be used for energy metabolism. More for myelin, membranes and acetylcholine formation, etc.. So yes fatty acids can help the CNS but is it NOT for energy. That is glucose and to a lesser extent ketones.

I agree adb12 is important. But adb12 has importance to the health of the mitochondria and peroxynitite removal. I don't dispute the elevated MMAs in Parkinson's, et al. But that does not say anything about the primary metabolic aspects of neurons. Not even close. Also why do you never bring up the high levels of microglial activation and inflammation now know to be signatures of most of the CNS diseases you listed. You focus exclusively it seems on the MMA levels. Why not the inflammation? Can't that tie back into adb12 / BH4 and peroxynitite removal and the low MMAs are a correlative finding?

As far as carnitine goes with the brain you cannot even ABSORB carnitine in the CNS unless either (a) it is acetyl-carnitne or (b) you have a very leaky BBB. However, if someone has a very leaky BBB, I have no idea how they will react to l-carnitine (note the fumarate will be long gone by the time anything gets past the leaky BBB). Will it be used as a primary pathway for energy metabolism? Dunno.

Again inflammation and microglial activation is elevated also. And I am sorry again to have to re-iterate this but ... without a leaky BBB (which admittedly may be a big component of all of this) you cannot absorb LCF in the brain. It does not cross a healthy BBB. It just doesn't. Now why the LCF has such a dramatic effect on the limbic system as you have observed, I do not know. If it is not an indirect effect through the periphery (which is not impossible given how there is a big chunk of the ANS living in your abdomen) or it is not due to a leaky BBB ... then I don't know why.

Btw I am not sure why you think I am dismissing anything. I am simply trying to understand things. Clinical trial and error is not enough for me being a physicist and bioinformatics professional. Sorry that is just the way I am built.

Nor did I intend my simple response about the Krebs cycle and brain metabolism to in any way be considered adversarial. In fact my intent was to SUPPORT your idea that mitochondria in the brain are relevant. Let me repeat that: I was supporting you.

I have no idea why Rich Vank would ever think mitochondria in the brain are not important for neuronal health. Of course they are. Is adb12 important? Sure. But your conjecture that adb12 is important BECAUSE of the MMA pathways alone is by no means a given. It simply is not going to be the primary adjunct to the Krebs cycle. It could be a block if too low but it will never be the main fuel ... that is all I was trying to say by those comments. Just like burning fatty acids is not the main fuel in the brain. If your only conclusion based on your clinical experiences and people's reaction to carnitine is that burning fatty acids in the brain will bolster the Krebs cycle or the MMA pathway being stimulated will power the TCA on its own ... well then let's just choose to disagree.

What is so wrong with theory? Theory and experiment go hand in hand. Again I don't doubt your observations. I also NEVER in this or any other posts challenged your deadlock quartet idea. I find it quite attractive. I am just trying to understand why things happen. Is that so bad? Engineering is great but civilization would not have gotten very far if there wasn't theory as well to work with it.

Anyways I already stated my points about adb12 and LCF with respect to the brain. L-carnitine is not absorbable through BBB unless the BBB is damaged ... which may very well be the case for many with CFS and is KNOWN to be the case with MS, ALS and is now being suspected with Parkinson's. The Omega 3s are important for sure. Ironically the DHA is a major component in BBB integrity. So ... maybe a leaky BBB is highly relevant to this discussion. Maybe people with a leaky BBB hyper-react to LCF at the limbic system level. Which if so means I am probably in for a rough ride since my Stiff Person Syndrome only occurs because of a leaky BBB, but that is a separate issue.

No argument. I already posted how biotin affects the Krebs cycle since there seemed to be some confusion on the forums about it. Biotin plays a critical role in the brain. How else do you think the pyruvate from glycolysis gets into the Krebs cycle in the brain? I also agree that biotin can really speed things up and so there is an important balance with other factors. No doubt. Definitely is a good avenue for further research. As would any of the critical cofactors for entry into the Krebs cycle. Biotin though may be of more importance due to its pivotal role in the brain. Btw biotin is also now believed to be a critical cofactor for glutamine synthetase. That could be huge for the brain function as well.

I am not sure why this even came up here. I have no clue why MCV is showing up here. I have no disagreement about your views of cycbl or hb12. Nor does what I am saying about the Krebs cycle and brain metabolism have anything whatsoever to do with cycbl or hb12 or their malignant use by the medical community. I am simply talking biochemistry. Ironically a new outsider reading your post would presume that I must disagree with everything that you propose. Huh? Far from that. So why all of this?

No one said you have to prove anything. Thought this was an open forum with dialog. Understanding is important to many of us. Again my comments were to SUPPORT your side of the argument you had with Rich Vank in that brain mitochondria are directly relevant to neuronal health.

Peace.

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Hi Dbkita,

Any misunderstandings of mine you can aid me in clearing up I appreciate.

Let’s go first at a general way to why I have the opinions on AdoCbl and LCF I do as regards the CNS.

First, when I get the symptoms/nutrients all up you will be able to see the order of repair. The peripheral nervous systems, all of them, appeared to largely heal during the time of MeCbl with basics, folic acid and veggie folate. I hadn’t started eating meat again at that point. Then in a series of trials I and many others have done. There is a clear distinction between CNS effect of MeCbl at 7.5mg or more absorbed via sublingual or subcutaneous injection (spread across hours of absorption). There is a similar but different response with the CNS with 7.5mg or more absorbed in the same way as MeCbl and most people who have one response have both. Noticeable body response to doses has to be gone in both cases as they are overwhelmingly strong compared to the CNS only response. They both exhibit marked CNS only effects that lesser doses do not. I do not know why LCF has about a 10:1 response rate as compared to ALCAR in all this. Then people with all the usual symptoms PLUS anxiety demonstrate hyper sensitive response in the limbic system specifically. There is no way that 500mcg of oral l-carnitine fumarate could have such a dramatic effect in only the limbic system if it were not getting there. I also know the feel of directly energized neurons though it doesn’t throw me into extreme limbic response. It is unmistakable. Anything that says l-carnitine fumarate can’t have a prompt and direct effect that ALCAR does not have is WRONG. How many times does it have to be demonstrated? Of course there is the opposite too, those with dramatic CNS effect of ALCAR but not of LCF.

Check out physiological neural psychology to see why I say limbic system, also that is where the damage is, or maybe inflammation and damage. I have raised that possibility of inflammation on the main description thread. 500mcg of LCF or freebase carnitine of any kind has no body response I am aware of or anybody is that I know of but it sure sets off the limbic system in people with the so-called “Parkinson’s personality” with dramatic and rapid results. I have no idea how it gets there or why so little has such a disproportionate effect. My body had a huge body response to LCF and having ALCAR and/or any other forms mixed in or instead of stopped the effectiveness 100%. I had a very mild CNS response to AdoCbl and who knows about CNS noticeable effect from LCF since it did not have the double threshold that the cobalamins have. However, SACD started recovering only AFTER I got the AdoCbl into my body at the CNS penetrating levels. This major CNS healing effect is noticeable in 1 hour or less when all factors are present. I had mood and personality changes at normal sublingual doses of MeCbl/AdoCbl but no healing of cord demyelinizations. Those required all four of the Deadlock Quartet in sufficient doses. And those are more of an equilibrium situation, breaking down and healing all the time in a slightly different pattern. If something occurs to shift towards a different equilibrium point in a month I lose some numbness (a painful path however) or it shifts towards more numbness (more comfortable) but makes me feel like I am wearing ski boots all the time.

No one said you have to prove anything. Thought this was an open forum with dialog. Understanding is important to many of us. Again my comments were to SUPPORT your side of the argument you had with Rich Vank in that brain mitochondria are directly relevant to neuronal

I think there is misunderstanding here. It is a very big difference in approach. You talked about to “prove” this or that. I can’t prove a thing. I can predict and demonstrate. That is a different thing. I was trying to make a distinction of my objectives. Rich was out to “prove” his theory. It requires a different approach. An engineering approach often doesn’t prove anything. I debugged this like I debug a computer program. I learn how to make it fail reliably and repeatedly at the same time I learn how to make it succeed reliably and repeatedly. In this I am a Roman engineer learning how to make domes and arches that don’t fall down, not figuring out how to build the twin towers via a different theory which introduced a whole new possible failure mode for skyscrapers. The Empire State Building didn’t collapse straight down when a bomber ran into it and burned. It didn’t collapse in any way. Granite is tough stuff.

The AMA etc says in essence “testing everybody for b12 is not cost effective as it only finds 1% of population and they are expensive to treat forever with all the comorbidities”. 100% of that is based on folic acid, CyCbl and HyCbl. There is zero expectation that anybody will actually heal or reduce expenses. So detecting and treating b12 deficiency is very difficult, expensive and not worthwhile as they won’t really get well anyway unless you define that as getting MCV< 102 these days and maintain serum cobalamin level at or above 300pg/ml just before the next injection or with oral CyCbl tablets. By these definitions it is a complete surprise that mecbl and AdoCbl are completely unpredictable based on CyCbl and HyCbl experience.

I used this as a spectacularly bad example of how different approaches have different results. The standard model research resulted in this travesty and the beliefs based upon the body of knowledge that is distorted by assumptions and preconceptions. My life was severely damaged, damn near destroyed and costing me almost everything, by the AMA’s approach. Everything about the above paragraph leads to the worst possible treatment being used for as few people as possible. It puts in place roadblocks to care that are insurmountable for most people. I come from a lifetime of experience in a mostly a managed care environment. We were all about removing the roadblocks to care.

Btw I am not sure why you think I am dismissing anything.

I misunderstood. I’m sure we both misunderstand much. That’s why we are having a fruitful dialog. Thankyou.

I am simply trying to understand things. Clinical trial and error is not enough for me being a physicist and bioinformatics professional. Sorry that is just the way I am built.

No apologies necessary for the way you are built or anything else. I end up doing the same quite often. I am 100% for understanding and find it stimulating to hash it out. Dialog is extremely valuable. I would not be here with what I have without Rich, and you by the way, and many before both of you, now as my understandings are progressing by the day. It is good to know. I looked up bioinformatics. I started HMO consulting the year the term was invented. I helped develop the basic ideas behind object oriented design and programming and medical record “data mining”. I was invited my Yourdon to do some writing for him. I crashed a month later and was quite unable to do anything for a year. I had to drop out of college 5 times for health reasons, the same ones I have been describing but at an earlier stage of deterioration. I started college at WPI (Yep, Whoopi Tech) as an engineering freshman. I had already selected physics as my major when I got mono. That was that for WPI.

Clinical trial and error is not enough for me

That is a major misunderstanding. There was nothing trial and error in what I did. Everything I did was based on journals and data mining the internet and the results of the trial and error practitioners, professional and otherwise. I did an N=1000 questionnaire development study. When I could no longer work I set out to solve my own problems and get well, and followed the clues, and I already had the first clue. I had a theory about liver extract concentrate and set out to duplicate it. I systematically tested brands until I found the effective forms and/or brands. There was nothing at all trial and error. It was targeted, hypothesized, experiment performed, understood and modified. It was very systematic titrations of through entire ranges. The normal model research has taken the beliefs about “b12” and “folate” so far from being predictive in any way as to what to expect from the Deadlock Quartet that I literally don’t know how to describe such a cognitive defect when applied to so many intelligent people. I see how it happened. I have lost faith in a sense in the whole model of research. In the 60s the term “group think” was invented. That doesn’t quite get at it. How in 80 years of research looking for and then working with substances, could they come to rely upon the worst possible form that has any effect at all, known as a mistake since 1959, known from the early 50s not to replicate concentrated liver extract except in the most minimal way. Folic acid I can see. Folic acid was the best they could do in 1942. Now we have Metafolin. That is progress. People are learning to use it. CyCbl? HyCbl? How can people be so blind for so long and go so far astray from what works. The incorrect assumptions from these three items corrupts understanding downstream. How could they not? They have made hundreds or probably thousands of deficiency symptoms and signs into incurable mystery diseases. I would think that would be of concern. I was dying. I couldn’t wait any longer. I had been waiting since 1979 thinking a mistaken Nobel Prize being the scandal of a century for causing millions of chronically ill people would surely get noticed and remedied. No such luck. Instead in the most bizarre twist chronic deficiency diseases have become enshrined as the standard. The FDA prohibits vitamin claims that they prevent deficiency diseases, obviously for good reasons.

What is so wrong with theory? Theory and experiment go hand in hand. Again I don't doubt your observations. I also NEVER in this or any other posts challenged your deadlock quartet idea. I find it quite attractive.

I think that it leads to a complete reconceptualization. And with lots of help, fill in some of the other less common branches, like the biotin.

Engineering is great but civilization would not have gotten very far if there wasn't theory as well to work with it.

Nothing at all wrong with theory. I engage in such at a different level. I work from theory but design from the bottom up or occasionally from the middle out. I determine what I the whole thing is about and then work from the database design up in general. My understanding is at a pragmatic level and pattern recognition. Please do dig in as deeply as you can. All this desperately needs to be understood. Right now the questions that I desperately need answered are:

1. What makes a 5 star MeCbl such?

2. What are the tests?

If either of the two theories I’ve heard are correct an NMR and mass spec should be able to do the job. I have no access or expertise in instrumental chemistry and don’t know anybody currently who does. I have frozen samples.

I agree theory is needed, and refinement and corrections over and over. Civilization wouldn’t have gotten very far without it. Fully agreed. The theory has gone very badly astray, like Galopping Gertie.

I just got “it”. I don’t speak biochemistry and I am using various analogies indicating a screwed up structure, or logic or assumptions and so on. I look at it as part of the gestalt that makes up our whole you might say holographic interpretative mechanism. I was saying wrong results can occur due to how something is thought as much what is thought. I’m sort of looking at it as a virtual Monte Carlo simulation in my head and then picking the path(s) that work(s). Maybe I’m practicing too much philosophy without a license in the wrong place. Yours and mine are quite different. As we continue we will both learn to translate better and better understanding

Not even close. Also why do you never bring up the high levels of microglial activation and inflammation now know to be signatures of most of the CNS diseases you listed. You focus exclusively it seems on the MMA levels. Why not the inflammation? Can't that tie back into adb12 / BH4 and peroxynitite removal and the low MMAs are a correlative finding?

I knew nothing about that. I haven’t filled in that piece of the puzzle yet. The CSF MMA, CSF Hcy and low CSF cobalamin are common factors across a range of diseases that all will likely react in differentiating, but predictable when recognized, ways dependent upon the specific damage each has for all sorts of secondary and tertiary deficiencies and other reasons. It sure could tie back to AdoCbl. High MMA in Parkinson’s and ALS, high Hcy in MS and ALS. So where does CSF MMA come from if not neuronal mitochondria utilizing AdoCbl and LCF, however it got there?

Again my comments were to SUPPORT your side of the argument you had with Rich Vank in that brain mitochondria are directly relevant to neuronal health.

Rich actually addressed all of this. Maybe not exactly in the way it was worded here. It is truly sad that he's not here and unable to respond. I really don't have time to dig up all his posts, but I think this covers enough.
The role of lecithin is to help with repair of cell membranes, especially mitochondrial membranes, which have been damaged by oxidative stress. I suspect that the damaged mito membranes are one of the main reasons why many PWMEs have found that recovering their energy status is one of the slowest aspects of recovery from ME/CFS.

I think that using it will help to bring the ATP production of the mitochondria up sooner, which will mean more energy.

In ME/CFS, the mitochondria are dysfunctional. This is shown particularly in the published paper of Myhill et al.

What can you do to improve this? Well, the mito dysfunction must be corrected. To do this, one has to lift the partial methylation cycle block, which will allow glutathione to rise. This will overcome the deficiencies in the substances needed by the mitochondria that require methylation for their synthesis, and it will also overcome the oxidative stress, which suppresses mito activity, and will also remove the toxins that have been deposited in the mitochondria and are blocking enzymes there. This is what the methylation protocols (discussed elsewhere on the forums) are designed to do.

Yes, they do. However, in my view, ME/CFS is also not fundamentally a mitochondrial disorder. The mitochondria are very much affected, but the fundamental problem, in my opinion, is in the metabolism upstream of them, too. Studying the mitochondrial dysfunction, as Myhill et al. have done, is very much a step in the right direction, though, in my opinion.

Why are the mitochondria dysfunctional in ME/CFS? The work that Dr. John McLaren Howard at Acumen Lab in the UK has done (note that he did the lab work in the Myhill et al. study) has identified many abnormalities in the mitochondria in ME/CFS. In my view, they can all be traced back to a vicious circle mechanism that involves a chronic combination of the following: 1. Depletion of glutathione as a result of some combination of a variety of possible stressors in a person who is genetically predisposed, 2. A functional deficiency of vitamin B12, resulting from lack of protection of it intracellularly by glutathione, 3. An inhibition or "partial block" of the enzyme methionine synthase in the methylation cycle as a result of lack of sufficient methyl B12, due to the B12 functional deficiency, 4. Draining of folate from the cells into the blood via the "methyl trap" mechanism, as a result of the partial block of methionine synthase, and 5. Chronic glutathione depletion as a result of the disruption of the sulfur metabolism that results from the partial block of methionine synthase, solidifying the vicious circle and making ME/CFS a chronic condition.

That's it in a nutshell. Nearly everything else in ME/CFS flows from this vicious circle mechanism. Even the effects of the pathogen infections can be traced back to this vicious circle, because of its influence on the immune system, making it dysfunctional and allowing infections to be perpetuated.

Considering the mitochondria specifically, the depletion of glutathione allows the rise in oxidative stress as well as rises in the body burdens of toxins. The oxidative stress impacts both the Krebs cycle (at aconitase) and the respiratory chain (at one of the cytochrome enzymes), downregulating their activities. The toxins block various enzymes in the mitochondria as well as the ADP-ATP transporter protein, and the act as adducts on the DNA. The lowering of ATP production that results from these actions interferes with the activity of the membrane ion pumps, and that disrupts the normal concentrations of the essential minerals in the mitochondria, including magnesium, calcium, zinc, and others. Lactic acid rises because of a shift to anaerobic metabolism that results from lack of sufficient ATP production by the mitochondria.

Furthermore, the partial block of methionine synthase lowers the capacity for carrying out methylation reactions in general, causing decreases in the rates of production of several metabolites that require methylation for their synthesis and are needed by the mitochondria, including creatine, choline, carnitine and coenzyme Q-10. All of these are low in ME/CFS.

In addition, the functional deficiency of vitamin B12 causes a deficiency of adenosyl B12 (in addition to the deficiency of methyl B12). Adenosyl B12 is needed to feed branched-chain amino acids, odd-chain fatty acids and other metabolites into the Krebs cycle to be used as fuel.

The point of this long discourse is to make the case that the mitochondria are also downstream victims of this basic vicious circle mechanism in the metabolism.

This type of biochemical analysis can be applied to other features of ME/CFS as well, and they can be shown to trace back to this vicious circle mechanism. Probably the issues in the brain and the gut are the most complicated to figure out in ME/CFS, because so many different biochemical abnormalities that all stem from this vicious circle converge in these organs, making the situation there very complex.

Rich actually addressed all of this. Maybe not exactly in the way it was worded here. It is truly sad that he's not here and unable to respond. I really don't have time to dig up all his posts, but I think this covers enough.
The role of lecithin is to help with repair of cell membranes, especially mitochondrial membranes, which have been damaged by oxidative stress. I suspect that the damaged mito membranes are one of the main reasons why many PWMEs have found that recovering their energy status is one of the slowest aspects of recovery from ME/CFS.

I think that using it will help to bring the ATP production of the mitochondria up sooner, which will mean more energy.

In ME/CFS, the mitochondria are dysfunctional. This is shown particularly in the published paper of Myhill et al.

What can you do to improve this? Well, the mito dysfunction must be corrected. To do this, one has to lift the partial methylation cycle block, which will allow glutathione to rise. This will overcome the deficiencies in the substances needed by the mitochondria that require methylation for their synthesis, and it will also overcome the oxidative stress, which suppresses mito activity, and will also remove the toxins that have been deposited in the mitochondria and are blocking enzymes there. This is what the methylation protocols (discussed elsewhere on the forums) are designed to do.

Yes, they do. However, in my view, ME/CFS is also not fundamentally a mitochondrial disorder. The mitochondria are very much affected, but the fundamental problem, in my opinion, is in the metabolism upstream of them, too. Studying the mitochondrial dysfunction, as Myhill et al. have done, is very much a step in the right direction, though, in my opinion.

Why are the mitochondria dysfunctional in ME/CFS? The work that Dr. John McLaren Howard at Acumen Lab in the UK has done (note that he did the lab work in the Myhill et al. study) has identified many abnormalities in the mitochondria in ME/CFS. In my view, they can all be traced back to a vicious circle mechanism that involves a chronic combination of the following: 1. Depletion of glutathione as a result of some combination of a variety of possible stressors in a person who is genetically predisposed, 2. A functional deficiency of vitamin B12, resulting from lack of protection of it intracellularly by glutathione, 3. An inhibition or "partial block" of the enzyme methionine synthase in the methylation cycle as a result of lack of sufficient methyl B12, due to the B12 functional deficiency, 4. Draining of folate from the cells into the blood via the "methyl trap" mechanism, as a result of the partial block of methionine synthase, and 5. Chronic glutathione depletion as a result of the disruption of the sulfur metabolism that results from the partial block of methionine synthase, solidifying the vicious circle and making ME/CFS a chronic condition.

That's it in a nutshell. Nearly everything else in ME/CFS flows from this vicious circle mechanism. Even the effects of the pathogen infections can be traced back to this vicious circle, because of its influence on the immune system, making it dysfunctional and allowing infections to be perpetuated.

Considering the mitochondria specifically, the depletion of glutathione allows the rise in oxidative stress as well as rises in the body burdens of toxins. The oxidative stress impacts both the Krebs cycle (at aconitase) and the respiratory chain (at one of the cytochrome enzymes), downregulating their activities. The toxins block various enzymes in the mitochondria as well as the ADP-ATP transporter protein, and the act as adducts on the DNA. The lowering of ATP production that results from these actions interferes with the activity of the membrane ion pumps, and that disrupts the normal concentrations of the essential minerals in the mitochondria, including magnesium, calcium, zinc, and others. Lactic acid rises because of a shift to anaerobic metabolism that results from lack of sufficient ATP production by the mitochondria.

Furthermore, the partial block of methionine synthase lowers the capacity for carrying out methylation reactions in general, causing decreases in the rates of production of several metabolites that require methylation for their synthesis and are needed by the mitochondria, including creatine, choline, carnitine and coenzyme Q-10. All of these are low in ME/CFS.

In addition, the functional deficiency of vitamin B12 causes a deficiency of adenosyl B12 (in addition to the deficiency of methyl B12). Adenosyl B12 is needed to feed branched-chain amino acids, odd-chain fatty acids and other metabolites into the Krebs cycle to be used as fuel.

The point of this long discourse is to make the case that the mitochondria are also downstream victims of this basic vicious circle mechanism in the metabolism.

This type of biochemical analysis can be applied to other features of ME/CFS as well, and they can be shown to trace back to this vicious circle mechanism. Probably the issues in the brain and the gut are the most complicated to figure out in ME/CFS, because so many different biochemical abnormalities that all stem from this vicious circle converge in these organs, making the situation there very complex.

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Hi Lotus,

Yes, we are in major agreement on most things but not several interpretations We arrived at such very similar ideas including lecithin, for very differring functions and reasons which will be apparent in an upcoming post I'm working on. As things like lecithin have lots of functions, there are lots of reasons to take it so we are likely both hust looking at different sides of the barn. One of our diasagrrements is a chicken and egg situation which is more probably correct in being called a mutual dependency cycle. Another is that I don't think a simplfied version is necessarily safe or effective which is something I have been trying to figure out, how to make it simple and safe and effective. And I think it comes down to various combinations of 6 fundamental mutally deadlocked problems rather than 1 at the base with multiple entry points rather than 1 entry point.

And the last post of his that I know of concerning MMA elevated in CSF because of neuronal mitochondria malfunction, as stated in a variety of research, was that it was a complete surprise to him so he sure didn't include this or anything branching from it. That's okay. That's how things happen. It's always a moving target as knowlege that was revolutionary becomes foundational. As he also stated several times, that I was covering a whole range of things he wasn't even attempting to deal with.

Partial methylation blocks in CNS and body are 2 of the 6 functional problms. Partial ATP blocks CNS and body(seems to match pretty well), and methyltrap (named 50 years or so ago) in body and CNS. And and they all depend upon fixing both methylation and ATP so as to get out of a very mutual deadlocked cycle.

Wow! Thanks for that piece of the puzzle! I did not know zinc was needed to convert beta-carotene to retinal! I had come to the conclusion that I was genetically unable to convert beta-carotene to Vitamin A but now it looks like it could be just another side-effect of my allergies using up all the damn zinc! And yes I do have eye issues...like a dry eye issue...when there is cold dry air which causes me allergies...all goes away when the temp rises above 32.
Do your eye issues go away as the weather improves?

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I can attest to the zinc copper relation, Danny mentioned. Increasing zinc actually raised my serum copper levels and ceruloplasminin though I take no copper. Before adding back in zinc while my zinc levels were 50% on the test, my copper and ceruloplasminin levels were dirt low. Be interesting to see my latest results in a couple of weeks.

Wonder if I can better tolerate vitamin A now. I think I used to take beta carotene. Something to revisit. Fortunately my diet provided 5000 IU a day on its own.

As far as I can tell, Deadlock Quartet blockage can cause endothelial dysfunction and inflammation. Have you ever heard of Robert Rinse and the “Rinse diet”? In the original articles in PREVENTION as well as peer review journals, he described the three forms of cholesterol. He is a physical chemist. The three forms he described was a hard melting point 300 deg C, a 100 deg C melting point form and a blood temperature liquid crystal form. The form being determined by the fatty acids in the body, i.e. lecithin, polyunsaturated fats, Vit C, b-complex and a few things. I have met several people for whom it worked exactly as described. That was what put me onto the fatty acids. His hypothesis is that the liquid crystal form literally protected the endothelial tissues in the blood vessels from eroding and damage and also the fatty acids and vitamins would convert the surface of the hard deposits to liquid form and they could melt away in 6 months, if you had all the right factors. http://www.quackwatch.org/13Hx/dr_rinse/brochure.pdfThis was the only place I was able to come up with a Rinse diet descrition. I made my own granola incorpoarating the yeast and lecithin etc. Now I'm a using lecitihin concentrate with more phosphatidyl choline. In trying to repair his severe angina with only a short life ahead, he was as desparate as any of us. He did what he knows. He was physical chemist, made a hypothesis about cholesterol and tested it. He though it was 3 differnt forms, not all one kind. He thought it had a normal and useful purpose, noit just artery cloggers. And he did all this during the 50s, the age of yellow solid transfat sticks on the table and the "healthful" shortening, Crisco (fat in your can) solid hydogenated vegetable oil. He was another victem medical approved disease promotor. Instead of induced deficieciency diseases he was loosing his life to transfats and the corruption of the the bodies fat.

Yes, we are in major agreement on most things but not several interpretations We arrived at such very similar ideas.

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And yet you quote dbkita 4 times in your last post saying"Again my comments were to SUPPORT your side of the argument you had with Rich Vank in that brain mitochondria are directly relevant to neuronal"
dbkita's statement was based on some claims you made about Rich in another thread that have yet to be substantiated. The quotes I provided from Rich address mitochondria, ATP, Krebs Cycle, adenosylcobalamin, and carnitine. As far as I know, Rich never spoke with you about your theory. dbkita is just accepting your word that it happened. Why would you drag dbkita and Rich into this to prove some tangetially related theory of yours? I'm glad carnitine fumarate works for you. I take it myself in fact. But to suggest that Rich is wrong because he doesn't have it in his methylation protocol seems absurd.

Another is that I don't think a simplfied version is necessarily safe or effective

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This is very puzzling since low potassium is much more common with your protocol than Rich's. Dr. Neil Nathan has used Rich's protocol with his patients and stated that it was safe.

As far as the effectiveness, this has also been proven by Dr. Neil Nathan both qualitatively and quantitatively. I can't imagine why you aren't convinced based on the results.http://www.prohealth.com/fibromyalgia/library/showarticle.cfm?libid=16138
To my delight, 70% of my patients had improved within 3 months, and 20% reported that they were much better, occasionally to the point of feeling cured.

This was exciting news. I was fortunate enough to obtain a private research grant to do a more formal study. With the assistance of Dr. Van Konynenburg and Dr. Yasko, along with input from Dr. Teitelbaum, who helped design the data collecting research tools, and Dr. Richard Deth, a well-known expert on methylation chemistry, we put this together.

The Project Went as Follows

• I took 30 patients (none of whom were part of the first pilot project), all of whom I had treated with Dr. Teitelbaum’s program, all of whom had made some progress (ranging from 30% to 70% improvement) but were still not where they needed to be health-wise.

• All had their methylation chemistry measured prior to the start of the supplements(3), and all took the supplements for the next 6 months, while we measured their chemistry and they reported on their health status throughout. All patients took exactly the same supplements.

• After six months, we individualized the patients’ treatment program based on their chemistry results, and continued to follow their progress and monitor their chemistry.

The Results Are Exciting(4)

Several important questions are addressed and answered:

1. First of all, do we find that fibromyalgia and chronic fatigue patients do, indeed, have abnormal methylation chemistry? YES

The initial methylation testing showed that:

• Every single patient had abnormal results.

• The average starting value of glutathione in our patients was 3.2 mmol/L (normal being 3.9-5.5 mmol/L)), and the average starting value for SAM (S-Adenosyl methionine, aka SAM-e, the major methylator) was 218 mmol/L (normal being 221-256 mmol/L).

• 83% started with low glutathione levels.

2. Can we demonstrate that taking these supplements raises those numbers into the normal range? YES

• After 3 months, the average glutathione level was 3.8 mmol/L

• After 6 months, the average glutathione level was 4.3 mmol/L

• After 9 months, the average glutathione level was 4.7 mmol/L, which represents a 47% improvement, and ALL patients now had a normal level.

• After 3 months, the average SAM level was 227 mmol/L

• After 6 months, the average SAM level was 238 mmol/L

• After 9 months, the average SAM level was 241 mmol/L, with only one patient not up into the normal range.

3. Does this rise in glutathione and SAM correlate with clinical improvement? YES

We had our patients rate 5 important areas of function on a 1-10 scale. This included energy, sleep, pain, cognitive function (memory, focus, concentration, and “brain fog”), and overall sense of well being.

We can demonstrate progressive improvement in all of these areas in most patients, over the 9 months of the study:

• Sleep improved from an initial score of 4.7 to 6.0, with 73% of patients reporting improvement.

• Energy improved from an initial score of 3.9 to 6.6, with 86% of patients reporting improvement.

• Pain improved from an initial score of 5 to 6.6, with 80% of patients reporting improvement.

• Cognitive function improved from an initial score of 5.0 to 6.3, with 73% reporting improvement.

• Overall sense of well being improved from 4.3 to 6.8, with 79% reporting improvement.

4. How much better were our patients? A LOT!

It took an average of 5 to 6 weeks before the supplements started to work, and we can clearly show that the longer patients stayed on this program, the better they got.

• Not everyone got better, but the vast majority (86%) improved.

• The average improvement was rated by our patients as 48%.

• And notably, 27% reported so much improvement that they now felt essentially well! Several who had not worked in over 5 years were able to resume full-time employment without difficulty.

Ok understood I don't dispute the observed effects. So now there is a big mystery for me.

ALCAR is much more blood brain penetratable. Carnitine is very controlled in transport across the BBB. Note to be clear I never said that carnitine is not in the brain nor does it not have any function there but that it could not be the primary source of fuel for the Krebs cycle. Beta oxidation in neurons is normally very low. Hence the emphasis on glucose or ketones.

Here for example is a paper (one of several) that discusses absorption, transport and beta oxidation in the brain involving carnitine.

Now maybe there is something special about LCF transport and the brain. Have not been able to track that down. Even then beta oxidation is meant to be only a small percentage of the energy process normally. Maybe even very small amounts of LCF have significant impact on the limbic system. That part of the brain is very complex. Again all I am saying is normal carnitine abundance and transport is carefully controlled in a normal healthy person. Another option is maybe LCF supplies an alternate pathway sometimes with tough startup consequences. Dunno.

Perhaps people who are hypersensitive have a blood brain barrier integrity problem. Blood brain barrier integrity is an often overlooked defect that has major implication to multiple neurological diseases. The irony is I have a very leaky BBB as either or precursor or a result of my rare autoimmune disease. I have had LCF before several years ago when I was at my worst. It did raise anxiety and insomnia but did not flip me out. I will know soon enough for the present when I have an available testing window (too many things going on at work at the moment to throw myself into the fire atm).

Where there is smoke there is fire. If there is damage in the CNS there is inflammation almost guaranteed.

I don't dispute that the MMA-succinyl COA pathway is important for mitochondrial health. But from everything I have researched it is not a primary source of fuel for the Krebs cycle. On the other hand Adb12 clearly has some profound impact on the entire body if one is deficient. I still think the Gorilla in the Room hypothesis could have enormous impact on the CNS just considering that effect alone.

Not sure if this relevant to LCF but I had stumbled onto this a little while ago since my maternal grandmother died from MS and one of my paternal aunts has MS. As an aside I also have two family members who died of ALS and myself with the Stiff Person Syndrome. So studying of neurological diseases, the functions of microglia, astrocytes, neurotransmitters, etc. has been a common topic of research for me for some time now sadly.

It is a pdf from Biogen Idec about the history of fumarate as a therapeutic and about dimethylfumarate, monomethylfumarate and their protective effect on neurons and then more recent investigational drugs.

Ok fair enough.

I said "Just because there are indications of low B12 in certain neurodegenerative diseases does not in any way prove that neuronal mitochondria make heavy use of the methymalonic pathway as a primary energy source."

I should not have used the word "prove". I apologize. Honestly we can't really prove anything at the moment. There are too many variables and too much complexity. But proof is not required. I should have said

" ... neurodegenerative diseases does NOT have to mean that neuronal mitochondria make heavy use of the methymalonic pathway as a primary energy source". There are other alternate explanations is all I am suggesting.

Understand I am not out to prove any theory. I have no theory. I am by no means Rich Vank. He was a great guy who helped a lot of people. My goal is perhaps self-centered. Like many on here I want to understand what is going on so I can make the best choices in terms of improving my health. If along the way my questions and knowledge help someone else also then that is great.

Unlike many on here I have an extremely rare automimmune disease so I have to be very careful about what changes I make. I am already a living testimonial which is outside the realm of my disease. By all accounts I should be stuck in a wheelchair by now with an intrathecal baclofen pump. On the other hand, eventually my disease will cripple and kill me that is inevitable. But in the mean time I want to have as much quality of life as I can for my wife and children and myself. If that is self centered, then so be it.

Fair enough. Just please realize it was not my intention to attack anything you said. I was simply stating what I know about brain energy metabolic processes. You don't need to convince me about the idiocy rampant in the medical community. I could tell you horror stories (as I suppose many on here could) about a decade worth of misdiagnosis and fighting with doctors to get to someone who could save my life. Not fun.

Misunderstanding is the beginning towards understanding as far as I am concerned. Humanity still knows very little about the natural world including how are bodies work. Even less about the human brain I might add.

Thank you for all the information, hypotheses and experiences you have shared. You have access to some wonderful information that quite frankly does not exist elsewhere.

My emphasis is more on the biophysical modeling of proteins. But I was also at the ground floor for a numbes of years developing algorithms for identifying novel genes during the genome gold rush of the mid 90s.

It is a small world. I almost went to WPI for undergraduate but ended up going to the Univ of Wisconsin-Madison. In hindsight my decline probably started at the end of college, was still not so bad I could not get my PhD in astrophysics but after a decade in biotech startups that was it. Everything was spent and everything collapsed in blinding pain.

That is great to know. I honestly commend your diligence.

Such idiocy is rampant in all scientific fields to one extent or another. The crime in medicine is how it directly harms people's lives. None of us respect health until we lose it. Those of us who have almost completely lost health, value it far beyond any need for pretentions or horse blinders or enormous egos as are otherwise encountered in all walks of life much to my eternal sadness. It is the sad state of our race quite frankly. Never attribute to malice what is otherwise explained by incompetence

Personally what I find attractive is you are talking about a merger between two of the most important biochemical processes in the body namely ATP production (aerobic respiration) and methylation (which affects gene expression among many other things). But I would add that there may be important effects involving the immune system / inflammation and others like blood brain barrier integrity for the CNS. While not as compact as the Deadlock quartet, they may explain some people's differing responses to increasing the flux through these two cycles (three if you add in the folate cycle).

To clarify, when you say "what are the tests", what for? For assessing a methyl b12 supplement?

See my distinction is this. For example, when I read up on numerous research articles about the limits on beta oxidation in neurons in a normal brain, that is no longer theory to me (of course maybe I misinterpreted something, Lord knows that has happened numerous times). Instead that is research information that any theory I might suggest I feel should embrace and encompass. Just like in physics when I was studying black holes and neutron stars. Any hypotheseses had to obey constraints placed on me by other research data.

Hehe understood. Trust me I have never stopped being a physicist regardless of my occupation. We are what we are, nothing more, nothing less.

Not even close. Also why do you never bring up the high levels of microglial activation and inflammation now know to be signatures of most of the CNS diseases you listed. You focus exclusively it seems on the MMA levels. Why not the inflammation? Can't that tie back into adb12 / BH4 and peroxynitite removal and the low MMAs are a correlative finding?

First I am not certain that neurons and glial cells process mitochondrial fuels the same way. I have to check on that. People often focus on the neurons for obvious reasons, but glial cells and microglia are extremely important and being strongly implicated in several neurological disorders.

Second, I am positive that mitochondria in the brain does use the MMA pathway. I never said that they didn't. Just like someone with high glutamate excitotoxicity probably amplifies the AKG input path. But again like I stated before, in a normal brain the primary fuel is glucose via pyruvate with (I am pretty sure) entry into the Krebs cycle via biotin and not via the beta oxidation path involving carnitine and acetyl COA. If someone can correct me on that aspect, I would be much obliged.

If I remember right, the brain consumes roughly 120 grams of glucose or more a day on average for a healthy person. My neuroendocrinologist used to say the brain needs three primary elements: (a) oxygen, (b) glucose, and (c) blood brain barrier integrity; in that order. A simplistic viewpoint but there is merit to it. When any one of those three get disrupted there is *bleep* to pay. I think long term deficiencies in the deadlock quartet and / or other factors like severe inflammation can and do disrupt those three factors causing ultimately terrible havoc for the person who is suffering.

No problem. I apologize for any misunderstanding as well. I probably should have been clearer in what I was writing, something that is hard to do when I am in a rush.

Take care.

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Hi Dbkita,

It is a small world. I almost went to WPI for undergraduate but ended up going to the Univ of Wisconsin-Madison. In hindsight my decline probably started at the end of college, was still not so bad I could not get my PhD in astrophysics but after a decade in biotech startups that was it. Everything was spent and everything collapsed in blinding pain.

That is great to know. I honestly commend your diligence.

WPI was amazing. This was back in 1966. Our big new computer (7090) was set for 1967 delivery when the new computer center was to be finished. We had just the most amazing toys. There was a full machine shop for making anything we wanted. There was a warehouse full of military surplus electronic junk that we could glean parts from. My roommate built a kilowatt power supply for his ham radio at a cost of $3 in small parts. He also built an automated maple syrup tap to pour off the hot syrup at exactly the right temperature for their sugarhouse back home. They were working on computer automation of the big turret lathes at the time. We had genuine old German physicists who had worked with Bohr and others who had escaped. The school had the most amazing collection of profs one could hope for. When the old chem building was being cleared out the mechanical analytical balances were going for $5 and a triple beam for $1. The large patch in the brickwork from when Goddard blew up his lab was still visible. He was almost run out of town on a rail at the time after his gasoline powered rockets came down and set cornfields on fire.

Not sure if this relevant to LCF but I had stumbled onto this a little while ago since my maternal grandmother died from MS and one of my paternal aunts has MS. As an aside I also have two family members who died of ALS and myself with the Stiff Person Syndrome. So studying of neurological diseases, the functions of microglia, astrocytes, neurotransmitters, etc. has been a common topic of research for me for some time now sadly.

I’m adding some family history here too. My paternal everything is unknown. My maternal grandfather died at 89 of MS and had regular b12 injections. My mother had colon cancer and survived. My half-sisters have lots of symptoms and one dropped over in the doctor’s office with a heart attack at 45. Being in the hospital was the only thing that saved her life. All my kids carry forward a requirement for the same set of nutrients but in differing ratios and frequencies.

Stiff Person Syndrome is something I came across a lot in my reading, looking by symptoms and b12. In references to SPS there is lots of b12 mention. SACD, like MS has demyelization; does SPS? Death from SACD is usually from paralysis, followed by diaphragm and heart paralysis. It might also be considered terminal exhaustion of the body’s ability to generate the ability to move biochemically. The old PA descriptions, and that would likely but not always be coupled with megaloblastic madness, are contradictory about the interpretation of what is happening in final stages. It’s “not supposed to happen” any more

A similarity between IF and parietal cell antibodies and high MCV and SPS and GAD antibodies. The hypothesis is that IF antibodies cause high MCV via b12 deficiency. Only one problem, high MCV is present long before IF and parietal cell antibodies which tends to show up the longer and worse high MCV is present. The percentage of those lacking GAD and IF/parietal-cell antibodies in their respective situation are about the same. I have no idea if that means anything at all, just something I noticed.

Ok understood I don't dispute the observed effects. So now there is a big mystery for me.

ALCAR is much more blood brain penetratable. Carnitine is very controlled in transport across the BBB. Note to be clear I never said that carnitine is not in the brain nor does it not have any function there but that it could not be the primary source of fuel for the Krebs cycle. Beta oxidation in neurons is normally very low. Hence the emphasis on glucose or ketones.

Endothelial dysfunction? Maybe, in a population without these deficiencies and problems ALCAR response would be different. I have no idea how or why there is so much difference. Also the liquid freebase carnitine from Jarrow (Sigma Tau manufactured) generally works well too. And truly it doesn’t concern me in the least what percentage it accounts for. Maybe that accounts for its very “local” effects as in the limbic system or maybe dorsal horns.

Under normal conditions, pain conduction begins with some noxious signal followed by an action potential carried by nociceptive (pain sensing) afferent neurons, which elicit excitatory postsynaptic potentials (EPSP) in the dorsal horn of the spinal cord. That message is then relayed to the cerebral cortex, where we translate those EPSPs into "pain". Since the discovery of astrocytic influence, our understanding of the conduction of pain has been dramatically complicated. Pain processing is no longer seen as a repetitive relay of signals from body to brain, but as a complex system that can be up- and down-regulated by a number of different factors. One factor at the forefront of recent research is in the pain-potentiating synapse located in the dorsal horn of the spinal cord and the role of astrocytes in encapsulating these synapses. Garrison and co-workers (Garrison, 1991)[full citation needed] were the first to suggest association when they found a correlation between astrocyte hypertrophy in the dorsal horn of the spinal cord and hypersensitivity to pain after peripheral nerve injury, typically considered an indicator of glial activation after injury. Astrocytes detect neuronal activity and can release chemical transmitters, which in turn control synaptic activity (Volters and Meldolesi, 2005; Haydon, 2001; Fellin, et al., 2006). In the past, hyperalgesia was thought to be modulated by the release of substance P and excitatory amino acids (EAA), such as glutamate, from the presynaptic afferent nerve terminals in the spinal cord dorsal horn. Subsequent activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid), NMDA (N-methyl-D-aspartate) and kainate subtypes of ionotropic glutamate receptors follows. It is the activation of these receptors that potentiates the pain signal up the spinal cord. This idea, although true, is an oversimplification of pain transduction. A litany of other neurotransmitter and neuromodulators, such as calcitonin gene-related peptide (CGRP), adenosine triphosphate (ATP), brain-derived neurotrophic factor (BDNF), somatostatin, vasoactive intestinal peptide (VIP), galanin, and vasopressin are all synthesized and released in response to noxious stimuli. In addition to each of these regulatory factors, several other interactions between pain-transmitting neurons and other neurons in the dorsal horn have added impact on pain pathways.

Two states of persistent pain

After persistent peripheral tissue damage there is a release of several factors from the injured tissue as well as in the spinal dorsal horn. These factors increase the responsiveness of the dorsal horn pain-projection neurons to ensuing stimuli, termed "spinal sensitization," thus amplifying the pain impulse to the brain. Release of glutamate, substance P, and calcitonin gene-related peptide (CGRP) mediates NMDAR activation (originally silent because it is plugged by Mg2+), thus aiding in depolarization of the postsynaptic pain-transmitting neurons (PTN). In addition, activation of IP3 signaling and MAPKs (mitogen-activated protein kinases) such as ERK and JNK, bring about an increase in the synthesis of inflammatory factors that alter glutamate transporter function. ERK also further activates AMPARs and NMDARs in neurons. Nociception is further sensitized by the association of ATP and substance P with their respective receptors, [[P2X3]], and neurokinin 1 receptor (NK1R), as well as activation of metabotropic glutamate receptors and release of BDNF. Persistent presence of glutamate in the synapse eventually results in dysregulation of GLT1 and GLAST, crucial transporters of glutamate into astrocytes. Ongoing excitation can also induce ERK and JNK activation, resulting in release of several inflammatory factors.

As noxious pain is sustained, spinal sensitization creates transcriptional changes in the neurons of the dorsal horn that lead to altered function for extended periods. Mobilization of Ca2+ from internal stores results from persistent synaptic activity and leads to the release of glutamate, ATP, tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2). Activated astrocytes are also a source of matrix metalloproteinase 2 (MMP2), which induces pro-IL-1β cleavage and sustains astrocyte activation. In this chronic signaling pathway, p38 is activated as a result of IL-1β signaling, and there is a presence of chemokines that trigger their receptors to become active. In response to nerve damage, heat shock proteins (HSP) are released and can bind to their respective TLRs, leading to further activation.

ter persistent peripheral tissue damage there is a release of several factors from the injured tissue as well as in the spinal dorsal horn. These factors increase the responsiveness of the dorsal horn pain-projection neurons to ensuing stimuli, termed "spinal sensitization," thus amplifying the pain impulse to the brain. Release of glutamate, substance P, and calcitonin gene-related peptide (CGRP) mediates NMDAR activation (originally silent because it is plugged by Mg2+), thus aiding in depolarization of the postsynaptic pain-transmitting neurons (PTN). In addition, activation of IP3 signaling and MAPKs (mitogen-activated protein kinases) such as ERK and JNK, bring about an increase in the synthesis of inflammatory factors that alter glutamate transporter function. ERK also further activates AMPARs and NMDARs in neurons. Nociception is further sensitized by the association of ATP and substance P with their respective receptors, [[P2X3]], and neurokinin 1 receptor (NK1R), as well as activation of metabotropic glutamate receptors and release of BDNF. Persistent presence of glutamate in the synapse eventually results in dysregulation of GLT1 and GLAST, crucial transporters of glutamate into astrocytes. Ongoing excitation can also induce ERK and JNK activation, resulting in release of several inflammatory factors.

As noxious pain is sustained, spinal sensitization creates transcriptional changes in the neurons of the dorsal horn that lead to altered function for extended periods. Mobilization of Ca2+ from internal stores results from persistent synaptic activity and leads to the release of glutamate, ATP, tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2). Activated astrocytes are also a source of matrix metalloproteinase 2 (MMP2), which induces pro-IL-1β cleavage and sustains astrocyte activation. In this chronic signaling pathway, p38 is activated as a result of IL-1β signaling, and there is a presence of chemokines that trigger their receptors to become active. In response to nerve damage, heat shock proteins (HSP) are released and can bind to their respective TLRs, leading to further activation.

In human vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium (the inner lining of blood vessels) and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or acting on) the endothelium.[1] Normal functions of endothelial cells include mediation of coagulation, platelet adhesion, immune function and control of volume and electrolyte content of the intravascular and extravascular spaces.

Endothelial dysfunction can result from and/or contribute to several disease processes, as occurs in hypertension, hypercholesterolaemia, diabetes, septic shock, Behcet's disease, and it can also result from environmental factors, such as from smoking tobacco products and exposure to air pollution.[2] Endothelial dysfunction is more prevalent in shift workers, a group known to have a higher risk for cardiovascular diseases.[3] Endothelial dysfunction is a major physiopathological mechanism that leads towards coronary artery disease, and other atherosclerotic diseases.[4]

As far as I can tell, Deadlock Quartet blockage can cause endothelial dysfunction and inflammation. Have you ever heard of Robert Rinse and the “Rinse diet”? In the original articles in PREVENTION as well as peer review journals, he described the three forms of cholesterol. He is a physical chemist. The three forms he described was a hard melting point 300 deg C, a 100 deg C melting point form and a blood temperature liquid crystal form. The form being determined by the fatty acids in the body, i.e. lecithin, polyunsaturated fats, Vit C, b-complex and a few things. I have met several people for whom it worked exactly as described. That was what put me onto the fatty acids. His hypothesis is that the liquid crystal form literally protected the endothelial tissues in the blood vessels from eroding and damage and also the fatty acids and vitamins would convert the surface of the hard deposits to liquid form and they could melt away in 6 months, if you had all the right factors. http://www.quackwatch.org/13Hx/dr_rinse/brochure.pdf

Now I had all those chronic pain problems. I still take 180mg of morphine daily for pain attendant to car wreck damage. I used to take Dilantin for the neurological pain and it worked very well. I used to take 2400mg of ibuprofen a day for inflammation. Both became totally unneeded in 1 year

I had direct damage to the dorsal horns from hyper-extension back in 1972 down the left side of my back. There is a pronounced asymmetry in my back and shoulder muscles

Background—Tissue edema and endothelial barrier dysfunction as observed in sepsis and acute lung injury carry high morbidity and mortality, but currently lack specific therapy. In a recent case-report, we described fast resolution of pulmonary edema upon treatment with the tyrosine kinase inhibitor imatinib through an unknown mechanism. Here, we explored the effect of imatinib on endothelial barrier dysfunction and edema formation.

Methods and Results—We evaluated the effect of imatinib on endothelial barrier function in vitro and in vivo. In human macro- and microvascular endothelial monolayers, imatinib attenuated endothelial barrier dysfunction induced by thrombin and histamine. siRNA knock-downs of the imatinib-sensitive kinases revealed that imatinib attenuates endothelial barrier dysfunction via inhibition of Abl-Related Gene kinase (Arg/Abl2), a previously unknown mediator of endothelial barrier dysfunction. Indeed, Arg was activated by endothelial stimulation with thrombin, histamine and VEGF. Imatinib limited Arg-mediated endothelial barrier dysfunction by enhancing Rac1 activity and enforcing adhesion of endothelial cells to the extra-cellular matrix. Using mouse models of vascular leakage as proof-of-concept, we found that pretreatment with imatinib protected against VEGF-induced vascular leakage in the skin, and effectively prevented edema formation in the lungs. In a murine model of sepsis imatinib treatment (6h and 18h after induction of sepsis) attenuated vascular leakage in the kidneys and the lungs (24h after induction of sepsis).

Histamine, and edema, appears to result from severe folate insufficiency/deficiency at least in the situations we have been discussing.

To clarify, when you say "what are the tests", what for? For assessing a methyl b12 supplement?

I and others can identify a really good MeCbl in the first injection of 7.5mg or more subcutaneously. It can take a week to identify a slightly lesser quality MeCbl and a month to identify the barely acceptable by in vivo trials. I am hoping that it is indeed a difference in the form of MeCbl by various bacterial cultures as some report as “known”. Other researchers think it is a mix of MeCbl and various others caused by errors in the refining and concentration process. The pharmacy uindependent analysis that is done for every batch from the compounding pharmacy I use says 100% MeCbl. There are tremendous differences from batch to batch. Preparing my own it is absolutely rock steady from prep batch to prep batch. But it isn’t good enough. I used 5 star mecbl for almost a year. I think a mass spec and an NMR could show us the differences. Maybe some other tests could be useful. If we could get an NMR signature of human CNS effective batches it would provide a way of testing for the best batches to buy.

why do you never bring up the high levels of microglial activation and inflammation now know to be signatures of most of the CNS diseases you listed. You focus exclusively it seems on the MMA levels. Why not the inflammation? Can't that tie back into adb12 / BH4 and peroxynitite removal and the low MMAs are a correlative finding?

First I am not certain that neurons and glial cells process mitochondrial fuels the same way. I have to check on that. People often focus on the neurons for obvious reasons, but glial cells and microglia are extremely important and being strongly implicated in several neurological disorders.

Sounds good to me. I didn’t know about them.

Just like in physics when I was studying black holes and neutron stars. Any hypotheseses had to obey constraints placed on me by other research data.

Hehe understood. Trust me I have never stopped being a physicist regardless of my occupation. We are what we are, nothing more, nothing less.

Black holes and neutron stars, you have to love them. You can’t leave them. After all what can reach through a General Products hull? I did a financial model that I named Black Hole back about 82-87. What it did was to model the conditions that would lead to a possibly worldwide bank collapse triggered by a real estate bubble collapsing or something similar. At the time I wrote it I thought it would be the Japanese real estate collapse. Who would believe such a thing could happen in this modern day of regulation. Ridiculous program. That one went down the black hole of no longer supported floppy formats. I do understand working within constraints unless you can show how they don’t apply.

" ... neurodegenerative diseases does NOT have to mean that neuronal mitochondria make heavy use of the methymalonic pathway as a primary energy source". There are other alternate explanations is all I am suggesting.

There are all sorts of ANDs involved and other explanations. I don’t really care and never claimed as a PRIMARY energy source and never even used that word. If I implied such, it was not intentional. I was just trying to get agreement that it wasn’t 100% glucose and that AdoCbl and LCF COULD make a difference unmatched by HyCbl, and that at least a part of that was ATP related. This is the first time the discussion has gone beyond that.

Personally what I find attractive is you are talking about a merger between two of the most important biochemical processes in the body namely ATP production (aerobic respiration) and methylation (which affects gene expression among many other things). But I would add that there may be important effects involving the immune system / inflammation and others like blood brain barrier integrity for the CNS. While not as compact as the Deadlock quartet, they may explain some people's differing responses to increasing the flux through these two cycles (three if you add in the folate cycle).

The immune system is strongly affected by folate and b12s. Almost all of it appears to correct over some number of years. Actual existing autoimmune damage doesn’t appear to be affected. Methyltrap appears to turn on the hyper responses of many kind;, asthma, allergies, MCS, and lack of resistance to viruses and bacteria. I’ve got to get that symptoms/nutrient analysis up.

Fair enough. Just please realize it was not my intention to attack anything you said. I was simply stating what I know about brain energy metabolic processes. You don't need to convince me about the idiocy rampant in the medical community. I could tell you horror stories (as I suppose many on here could) about a decade worth of misdiagnosis and fighting with doctors to get to someone who could save my life. Not fun.

Not fun at all. I know exactly what that is like. And so do a sizable percentage know the frustration. I found the emotional elevator of expectations and hopes and dreams always being crashed too much to deal with.

"Again my comments were to SUPPORT your side of the argument you had with Rich Vank in that brain mitochondria are directly relevant to neuronal"

dbkita's statement was based on some claims you made about Rich in another thread that have yet to be substantiated. The quotes I provided from Rich address mitochondria, ATP, Krebs Cycle, adenosylcobalamin, and carnitine. As far as I know, Rich never spoke with you about your theory. dbkita is just accepting your word that it happened. Why would you drag dbkita and Rich into this to prove some tangetially related theory of yours? I'm glad carnitine fumarate works for you. I take it myself in fact. But to suggest that Rich is wrong because he doesn't have it in his methylation protocol seems absurd.

This is very puzzling since low potassium is much more common with your protocol than Rich's. Dr. Neil Nathan has used Rich's protocol with his patients and stated that it was safe.

As far as the effectiveness, this has also been proven by Dr. Neil Nathan both qualitatively and quantitatively. I can't imagine why you aren't convinced based on the results.

To my delight, 70% of my patients had improved within 3 months, and 20% reported that they were much better, occasionally to the point of feeling cured.

This was exciting news. I was fortunate enough to obtain a private research grant to do a more formal study. With the assistance of Dr. Van Konynenburg and Dr. Yasko, along with input from Dr. Teitelbaum, who helped design the data collecting research tools, and Dr. Richard Deth, a well-known expert on methylation chemistry, we put this together.

The Project Went as Follows

• I took 30 patients (none of whom were part of the first pilot project), all of whom I had treated with Dr. Teitelbaum’s program, all of whom had made some progress (ranging from 30% to 70% improvement) but were still not where they needed to be health-wise.

• All had their methylation chemistry measured prior to the start of the supplements(3), and all took the supplements for the next 6 months, while we measured their chemistry and they reported on their health status throughout. All patients took exactly the same supplements.

• After six months, we individualized the patients’ treatment program based on their chemistry results, and continued to follow their progress and monitor their chemistry.

The Results Are Exciting(4)

Several important questions are addressed and answered:

1. First of all, do we find that fibromyalgia and chronic fatigue patients do, indeed, have abnormal methylation chemistry? YES

The initial methylation testing showed that:

• Every single patient had abnormal results.

• The average starting value of glutathione in our patients was 3.2 mmol/L (normal being 3.9-5.5 mmol/L)), and the average starting value for SAM (S-Adenosyl methionine, aka SAM-e, the major methylator) was 218 mmol/L (normal being 221-256 mmol/L).

• 83% started with low glutathione levels.

2. Can we demonstrate that taking these supplements raises those numbers into the normal range? YES

• After 3 months, the average glutathione level was 3.8 mmol/L

• After 6 months, the average glutathione level was 4.3 mmol/L

• After 9 months, the average glutathione level was 4.7 mmol/L, which represents a 47% improvement, and ALL patients now had a normal level.

• After 3 months, the average SAM level was 227 mmol/L

• After 6 months, the average SAM level was 238 mmol/L

• After 9 months, the average SAM level was 241 mmol/L, with only one patient not up into the normal range.

3. Does this rise in glutathione and SAM correlate with clinical improvement? YES

We had our patients rate 5 important areas of function on a 1-10 scale. This included energy, sleep, pain, cognitive function (memory, focus, concentration, and “brain fog”), and overall sense of well being.

We can demonstrate progressive improvement in all of these areas in most patients, over the 9 months of the study:

• Sleep improved from an initial score of 4.7 to 6.0, with 73% of patients reporting improvement.

• Energy improved from an initial score of 3.9 to 6.6, with 86% of patients reporting improvement.

• Pain improved from an initial score of 5 to 6.6, with 80% of patients reporting improvement.

• Cognitive function improved from an initial score of 5.0 to 6.3, with 73% reporting improvement.

• Overall sense of well being improved from 4.3 to 6.8, with 79% reporting improvement.

4. How much better were our patients? A LOT!

It took an average of 5 to 6 weeks before the supplements started to work, and we can clearly show that the longer patients stayed on this program, the better they got.

• Not everyone got better, but the vast majority (86%) improved.

• The average improvement was rated by our patients as 48%.

• And notably, 27% reported so much improvement that they now felt essentially well! Several who had not worked in over 5 years were able to resume full-time employment without difficulty.

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Hi Lotus,

dbkita's statement was based on some claims you made about Rich in another thread that have yet to be substantiated. The quotes I provided from Rich address mitochondria, ATP, Krebs Cycle, adenosylcobalamin, and carnitine.

But not the mitochondrial dysfunctions and effects and damage in the brain and cord.

As far as I know, Rich never spoke with you about your theory.

Why should you know? Why would you expect to know? Did he keep you up to date on everybody he talked with, had private correspondence with and exchanged data with? You obviously haven’t read (or maybe not remember) even everything he posted concerning these matters. Get real.

dbkita is just accepting your word that it happened.

Rich did to. I accept Rich’s word and Dbkita’s word, and yours for that matter and everybody posting here. I accept Rich as an honest researcher whom I would not have hesitated to invite into a suitable project, if one had come up. I would never expect him to lie or invent data. He didn’t expect that of me either. You seem ready enough to project lying onto others. I assume that folks are doing the best they can to be accurate about these things that matter very much to them about things that happened. None of us have any reason to lie. I’ve saved my life and healed myself. I don’t expect to make one red cent from this whole thing except for maybe consulting for some group health entity and setting up screening questionnaires and data mining patterns, and such. I doubt that there is anybody posting here that can afford to hire me as a consultant. We are all working towards a common goal, healing from this miserable set of conditions. We might have mistaken interpretations, but interpretations of what happened are not what happened. Don’t confuse the interpretation for the actuality. The map is not the territory. What I don’t accept are all the inferences, judgments, conclusions and logical structures. He was PUZZLED by it because he hadn’t considered that yet and it ran counter to understandings what he had built his logic system on. Things were in progress. He was going to see if he could get the raw data by each person from Dr Nathan so I could put it through the pattern matching analysis rather than statistical analysis. The purpose was to increase understanding, for both of us.

Why would you drag dbkita and Rich into this to prove some tangetially related theory of yours? I'm glad carnitine fumarate works for you. I take it myself in fact. But to suggest that Rich is wrong because he doesn't have it in his methylation protocol seems absurd.

You sound really off the wall here to me. Rich himself in several posts, which you could read if anybody can succeed in finding them, made it very clear that what I was doing was casting a much wider, and less specific, net. I NEVER suggested RICH was wrong. That is your invention. You are being absurd in this. I said a few specific things are incorrect. That is how understanding advances. I take “partial methylation block” as essentially correct and have adopted the terminology for that portion of things. I also posted about one of the videos where Rich described paradoxical folate deficiency but doesn’t use the word paradoxical.

This is very puzzling since low potassium is much more common with your protocol than Rich's. Dr. Neil Nathan has used Rich's protocol with his patients and stated that it was safe.[

Yes, i is. It is also very predictable and thereby manageable. In designing systems it is desirable to be able to predict where “variances” are going to occur, arrange things so they happen predictably with a known solution, to have a fail safe mode rather than ignore it, call it and pretend it is something else when it happens. My ex-wife told me that the doc was very alarmed when her hematocrit was 6 and with high MCV. So was I. She has started the vitamins and is going for other tests to look for bleeding. It is quite predictable that she will need potassium. Should she not be told that so as make her to take her chances? Which is more dangerous, letting her be taken by surprise or to have the potassium on hand.

Would you rather have it sneak up on you x% of the time at unpredictable times and be totally unprepared for it or have it happen as an expected flag that healing has turned on. THAT comes from 60 years of b12 research, the association of Hypokalemia with red blood cell formation starting. That isn’t my hypothesis. This stands on the shoulders of hundreds of researchers over 60 years. That it was so infrequent was because they used HyCbl and Cycbl and these are only about 1% as effective as MeCbl/AdoCbl and results in Hypokalemia about 1% of the time according to an awful lot of research. It was NEVER considered a detrimental effect. Instead it was considered proof positive that cell formation had started in a big way, or so thought many researchers. Then of course the person is told to take potassium. The dangerous time release form of potassium is “Only for those who are unable to comply with the frequent dosing requirements of oral potassium” Why are you trying so hard to paint it as something terrible to be avoided. Hypokalemia is predictable and for most people easily treatable. The people that had it in the studies were having the best responses. Did you think I made this up or am lying to you about it?

Avoiding the hypokalemia appears to avoid major healing startup. The people who get Hypokalemia have lots of things wrong and it appears to happen a few days after a person exits methyltrap, but that is a very approximate correlation. I set out to solve the neurological disease problems, not CFS/ME/FMS. Those were names we were called, not diagnosis. There were “yuppie flu” and “imaginary women’s diseases” , All In Your Head, conversion disorder, “medical students disease”, hypochondria, psychosomatic illnesses. You know those if you have been at this long enough. The partial methylation block is all about defining these things as a real disease. So are the additions I’m describing.

As far as the effectiveness, this has also been proven by Dr. Neil Nathan both qualitatively and quantitatively. I can't imagine why you aren't convinced based on the results.

I accept the results. I interpret them differently. He was working towards getting the raw data for a different kind of analysis that I had already done on processed data on a group basis where a lot of detail is lumped together. The analysis, if it worked out well, would have shown what was missing by what wasn’t helped and the nutrients possible involved. I also know how reports are written, you show all the improvements. There were plenty of “improvements”, a relative term.

I can attest to the zinc copper relation, Danny mentioned. Increasing zinc actually raised my serum copper levels and ceruloplasminin though I take no copper. Before adding back in zinc while my zinc levels were 50% on the test, my copper and ceruloplasminin levels were dirt low. Be interesting to see my latest results in a couple of weeks.

Wonder if I can better tolerate vitamin A now. I think I used to take beta carotene. Something to revisit. Fortunately my diet provided 5000 IU a day on its own.

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Hi Dbkita,

I found a substantial difference in titrating from 15mg/day to 65mg/day of zinc and 1mg of copper in the multi mineraql that gives me 15mg of zinc. Too much copper can cause all sorts of problems but I have no idea how much is too much or what effecfts it has.

I was taking for a while really large amounts of fish oil (Nordic Naturals liquid form 1 tbsp = 3 tspns per day).
I was getting like 1800 mg of DHA for example. The fish oil really nails my GI tract (gas, minor reflux, and lower bowel issues). Also made me very tired. I am still trying to figure out the best balance for my EFAs. I don't think the A in it was much of the issue.

However, I was on 20,000 IU vitamin A for a long time (also with 50K IU vit D three days a week) about two years ago. That combination induced massive fatigue and even low blood sugar problems (which I learned later they can both cause at high levels of intake). Since then I have consigned my self to smaller doses of vitamin D (still suffer the active - inactive D inversion suggestion inflammation) and little to no vitamin A (I get 5000 IU in my paleolithic diet).

Even this summer, a dose of 5000 IU vitamin A made me just feel more foggy, more fatigued, etc. Both vitamin D and A in the gut stimulate the immune system. However, I may be in a better place to tolerate the A now. The D is still an issue with the inversion. I am awaiting some new labs to help guide me in that respect. Fortunately my actual vitamin A serum levels are like 70% in the range. Then again vitamin A serum levels are notorious for not telling you squat about how much A you need or don't need.

I was taking for a while really large amounts of fish oil (Nordic Naturals liquid form 1 tbsp = 3 tspns per day).
I was getting like 1800 mg of DHA for example. The fish oil really nails my GI tract (gas, minor reflux, and lower bowel issues). Also made me very tired. I am still trying to figure out the best balance for my EFAs. I don't think the A in it was much of the issue.

However, I was on 20,000 IU vitamin A for a long time (also with 50K IU vit D three days a week) about two years ago. That combination induced massive fatigue and even low blood sugar problems (which I learned later they can both cause at high levels of intake). Since then I have consigned my self to smaller doses of vitamin D (still suffer the active - inactive D inversion suggestion inflammation) and little to no vitamin A (I get 5000 IU in my paleolithic diet).

Even this summer, a dose of 5000 IU vitamin A made me just feel more foggy, more fatigued, etc. Both vitamin D and A in the gut stimulate the immune system. However, I may be in a better place to tolerate the A now. The D is still an issue with the inversion. I am awaiting some new labs to help guide me in that respect. Fortunately my actual vitamin A serum levels are like 70% in the range. Then again vitamin A serum levels are notorious for not telling you squat about how much A you need or don't need.

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Hi Dbkita,

I misstarted whaty I meant. I meant have you tried fish liver oil A? Interesting on the fish oil though.

In this post this is a list of symptoms that are mine, and others experience of these nutritional items in relieving their symptoms, and in a very few instances reflect research and successful practice, such as p5p for Hcy and Liver extract studies of several disorders in old journals. In some instances the same symptoms might have different combinations of nutrients.

I was taking for a while really large amounts of fish oil (Nordic Naturals liquid form 1 tbsp = 3 tspns per day).
I was getting like 1800 mg of DHA for example. The fish oil really nails my GI tract (gas, minor reflux, and lower bowel issues). Also made me very tired. I am still trying to figure out the best balance for my EFAs. I don't think the A in it was much of the issue.

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One thing to be aware is that EPA inhibits the HPA. DHA doesn't, though. I have heard many complaints of fatigue on high EPA doses.